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La serina es un ligando natural y un activador alostérico de la piruvato quinasa M2
Barbara Chaneton1, Petra Hillmann2, Liang Zheng1
1Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow, G61 1BD, Scotland, United Kingdom.
Nature
|October 16, 2012
Resumen
Las células cancerosas Las células cancerosas.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología celular Biología celular.
- Las vías metabólicas.
Sus antecedentes:
- Las células cancerosas muestran distintos fenotipos metabólicos cruciales para el crecimiento.
- La sobreexpresión de la piruvato quinasa M2 (PKM2) y la dependencia de la biosíntesis serina/glicina son las claves.
- La interacción entre la actividad de PKM2 y la síntesis de serina no se entiende completamente.
Objetivo del estudio:
- Para aclarar la relación mecánica entre la actividad de PKM2 y la biosíntesis de la serina de novo.
- Para investigar el papel de la serina en la regulación de la función de PKM2 en las células cancerosas.
Principales métodos:
- Análisis bioquímicos para medir la actividad de PKM2.
- Experimentos celulares que involucran la privación de serina y la suplementación.
- Análisis del flujo metabólico para rastrear el carbono derivado de la glucosa.
Principales resultados:
- La serina se une directamente a la PKM2 humana y la activa.
- La actividad de PKM2 disminuye significativamente tras la privación de serina en las células cancerosas.
- La actividad reducida de PKM2 redirige el piruvato a las mitocondrias y mejora la biosíntesis de serina.
Conclusiones:
- Un nuevo mecanismo parecido al reostato vincula la actividad de PKM2 y la biosíntesis de serina.
- Esta reprogramación metabólica apoya la proliferación de células cancerosas bajo la disponibilidad de nutrientes.
- Dirigirse a esta vía podría ofrecer nuevas estrategias terapéuticas para el cáncer.
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